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The role of spatial embedding in mouse brain networks constructed from diffusion tractography and tracer injections.

ABSTRACT: Diffusion MRI tractography is the only noninvasive method to measure the structural connectome in humans. However, recent validation studies have revealed limitations of modern tractography approaches, which lead to significant mistracking caused in part by local uncertainties in fiber orientations that accumulate to produce larger errors for longer streamlines. Characterizing the role of this length bias in tractography is complicated by the true underlying contribution of spatial embedding to brain topology. In this work, we compare graphs constructed with ex vivo tractography data in mice and neural tracer data from the Allen Mouse Brain Connectivity Atlas to random geometric surrogate graphs which preserve the low-order distance effects from each modality in order to quantify the role of geometry in various network properties. We find that geometry plays a substantially larger role in determining the topology of graphs produced by tractography than graphs produced by tracers. Tractography underestimates weights at long distances compared to neural tracers, which leads tractography to place network hubs close to the geometric center of the brain, as do corresponding tractography-derived random geometric surrogates, while tracer graphs place hubs further into peripheral areas of the cortex. We also explore the role of spatial embedding in modular structure, network efficiency and other topological measures in both modalities. Throughout, we compare the use of two different tractography streamline node assignment strategies and find that the overall differences between tractography approaches are small relative to the differences between tractography- and tracer-derived graphs. These analyses help quantify geometric biases inherent to tractography and promote the use of geometric benchmarking in future tractography validation efforts.

SUBMITTER: Trinkle S

PROVIDER: S-EPMC8611903 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Schizophrenia is a heterogenous neuropsychiatric disorder with varying degrees of altered connectivity in a wide range of brain areas. Network analysis using graph theory allows researchers to integrate and quantify relationships between widespread changes in a network system. This study examined the organization of brain structural networks by applying diffusion MRI, probabilistic tractography, and network analysis to 48 schizophrenia patients and 24 healthy controls. T1-weighted MR images obtained from all participants were parcellated into 87 regions of interests (ROIs) according to a prior anatomical template and registered to diffusion-weighted images (DWI) of the same subjects. Probabilistic tractography was performed to obtain sets of white matter tracts between any two ROIs and determine the connection probabilities between them. Connectivity matrices were constructed using these estimated connectivity probabilities, and several network properties related to network effectiveness were calculated. Global efficiency, local efficiency, clustering coefficient, and mean connectivity strength were significantly lower in schizophrenia patients (p = 0.042, p = 0.011, p = 0.013, p = 0.046). Mean betweenness centrality was significantly higher in schizophrenia (p = 0.041). Comparisons of node wise properties showed trends toward differences in several brain regions. Nodal local efficiency was consistently lower in the basal ganglia, frontal, temporal, cingulate, diencephalon, and precuneus regions in the schizophrenia group. Inter-group differences in nodal degree and nodal betweenness centrality varied by region and showed inconsistent results. Robustness was not significantly different between the study groups. Significant positive correlations were found between t-score of color trails test part-1 and local efficiency and mean connectivity strength in the patient group. The findings of this study suggest that schizophrenia results in deterioration of the global network organization of the brain and reduced ability for information processing.

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The role of spatial embedding in mouse brain networks constructed from diffusion tractography and tracer injections.

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